Neuropeptide Y attenuates cardiac remodeling and deterioration of function following myocardial infarction.

Abstract

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.

• Authors: Yu-Yan Qin, Xiao-Ru Huang, Jian Zhang, Wenjing Wu, Junzhe Chen, Song Wan, Xi-Yong Yu, Hui-Yao Lan
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 30 Issue 2 Pg. 881-897 (02 02 2022) ISSN: 1525-0024 [Electronic] United States
• PMID: 34628054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Neuropeptide Y

Topics

• Animals
• Humans
• Mice
• Mice, Knockout
• Myocardial Infarction (blood, genetics, metabolism)
• Neuropeptide Y (blood, genetics)
• Ventricular Remodeling